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Int J Mol Sci ; 19(11)2018 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-30423942

RESUMEN

The development of new and better implant materials adapted to osteoporotic bone is still urgently required. Therefore, osteoporotic muscarinic acetylcholine receptor M3 (M3 mAChR) knockout (KO) and corresponding wild type (WT) mice underwent osteotomy in the distal femoral metaphysis. Fracture gaps were filled with a pasty α-tricalcium phosphate (α-TCP)-based hydroxyapatite (HA)-forming bone cement containing mesoporous bioactive CaP-SiO2 glass particles (cement/MBG composite) with or without Brain-Derived Neurotrophic Factor (BDNF) and healing analyzed after 35 days. Histologically, bone formation was significantly increased in WT mice that received the BDNF-functionalized cement/MBG composite compared to control WT mice without BDNF. Cement/MBG composite without BDNF increased bone formation in M3 mAChR KO mice compared to equally treated WT mice. Mass spectrometric imaging showed that the BDNF-functionalized cement/MBG composite implanted in M3 mAChR KO mice was infiltrated by newly formed tissue. Leukocyte numbers were significantly lower in M3 mAChR KO mice treated with BDNF-functionalized cement/MBG composite compared to controls without BDNF. C-reactive protein (CRP) concentrations were significantly lower in M3 mAChR KO mice that received the cement/MBG composite without BDNF when compared to WT mice treated the same. Whereas alkaline phosphatase (ALP) concentrations in callus were significantly increased in M3 mAChR KO mice, ALP activity was significantly higher in WT mice. Due to a stronger effect of BDNF in non osteoporotic mice, higher BDNF concentrations might be needed for osteoporotic fracture healing. Nevertheless, the BDNF-functionalized cement/MBG composite promoted fracture healing in non osteoporotic bone.


Asunto(s)
Cementos para Huesos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/uso terapéutico , Fémur/patología , Curación de Fractura/efectos de los fármacos , Vidrio/química , Fracturas Osteoporóticas/tratamiento farmacológico , Fosfatasa Alcalina/metabolismo , Animales , Cementos para Huesos/farmacología , Callo Óseo/efectos de los fármacos , Callo Óseo/enzimología , Callo Óseo/patología , Factor Neurotrófico Derivado del Encéfalo/farmacología , Proteína C-Reactiva/metabolismo , Modelos Animales de Enfermedad , Femenino , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados , Fracturas Osteoporóticas/sangre , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/patología , Porosidad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Muscarínico M3/metabolismo , Espectrometría por Rayos X , Microtomografía por Rayos X
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